Rays and arrays: the transcriptional program in the response of human epidermal keratinocytes to UVB illumination

The epidermis, our first line of defense from ultraviolet (UV) light, bears the majority of photodamage, which results in skin thinning, wrinkling, ke ratosis, and malignancy. Hypothesizing that skin has specific mechanisms to protect itself and the organism from UV damage, we used DNA arrays to foll ow UV-caused gene expression changes in epidermal keratinocytes. Of the 6,8 00 genes examined, UV regulates the expression of at least 198. Three waves of changes in gene expression can be distinguished, 0.5-2, 4-8, and 16-24 h after illumination. The first contains transcription factors, signal tran sducing, and cytoskeletal proteins that change cell phenotype from a normal , fast-growing cell to an activated, paused cell. The second contains secre ted growth factors, cytokines, and chemokines; keratinocytes, having change d their own physiology, alert the surrounding tissues to the UV damage. The third wave contains components of the cornified envelope, as keratinocytes enhance the epidermal protective covering and, simultaneously, terminally differentiate and die, removing a carcinogenic threat. UV also induces the expression of mitochondrial proteins that provide additional energy, and th e enzymes that synthesize raw materials for DNA repair. Using a novel skin organ culture model, we demonstrated that the UV-induced changes detected i n keratinocyte cultures also occur in human epidermis in vivo.